Long non-coding RNA MEG3 regulates proliferation, apoptosis, and autophagy and is associated with prognosis in glioma

J Neurooncol. 2018 Nov;140(2):281-288. doi: 10.1007/s11060-018-2874-9. Epub 2018 Oct 3.

Abstract

Purpose: Accumulating evidence indicates that dysregulated long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis and cancer progression. LncRNA-maternally expressed gene 3 (MEG3) has been shown to be involved in the initiation and development of several cancers, including glioma. However, the clinical prognostic value of MEG3 in glioma has not yet been fully elucidated.

Methods: The expression levels of MEG3 were detected in 79 glioma tissues and adjacent normal brain tissues, as well as, glioma cells and normal human astrocytes by qRT-PCR. Kaplan-Meier and Cox regression methods were utilized for the survival analysis. MTT assay, flow cytometry, and immunofluorescence assay were carried out to detect the impact of MEG3 on glioma cell proliferation, apoptosis, and autophagy.

Result: The current results showed that MEG3 expression was significantly downregulated in glioma tissues and cell line and negatively correlated with WHO grade in glioma patients. Low MEG3 expression was significantly associated with the advanced WHO grade, low Karnofsky performance score (KPS), IDH wild-type, and tumor recurrence. Patients displaying a low expression of MEG3 contributed to poor overall survival. The downregulated level of MEG3, advanced WHO grade, low KPS, IDH wild-type, and tumor recurrence were independent poor prognostic indicators in glioma patients. The in vitro experiments demonstrated that the MEG3 overexpression remarkably suppressed the proliferation while facilitating apoptosis and autophagy in glioma cells.

Conclusions: These findings indicated a critical role of MEG3 in glioma cell proliferation, apoptosis, and autophagy. Also, the gene was found to be significantly associated with the prognosis in glioma patients. Thus, it might provide a new target for predicting prognosis and therapeutic intervention in glioma.

Keywords: Apoptosis; Autophagy; Glioma; LncRNAs; MEG3; Prognosis; Proliferation.

MeSH terms

  • Apoptosis / physiology*
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Autophagy / physiology*
  • Biomarkers, Tumor / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Long Noncoding / metabolism*

Substances

  • Biomarkers, Tumor
  • MEG3 non-coding RNA, human
  • RNA, Long Noncoding